PROJECT SUMMARY Advances in molecular understanding of the process of carcinogenesis have led to the study of an increasing number of agents to intercept the early phases of cancer development, including the recent interest in immunoprevention. The overall objective of University of Arizona Cancer Prevention Clinical Trials Network (UA CP-CTNet) is to perform early phase clinical trials to evaluate the biologic effects of putative preventive agents and to determine clinically relevant correlates in order to identify agents with good safety profiles and preliminary efficacy for definitive Phase III trials. The UA CP-CTNet consists of a team of physicians from diverse specialties, statisticians, clinical staff, data managers, pathologists, translational scientists, and other personnel with extensive experience in early phase clinical trials of cancer preventive agents and in translational research in various organ sites. Specifically, the UA CP-CTNet will: ? Efficiently design and conduct Phase 0/I/II clinical trials to assess the cancer preventive potential of repurposed drugs that affect multiple chronic diseases, well-characterized nutraceutical agents, regional/topical drug delivery, and immune modulators, identified from translational research, epidemiological studies, and/or clinical research. ? Characterize the clinical activity and biological effects of putative cancer preventive agents on their defined molecular/biochemical targets, the immune surveillance network, surrogate endpoints associated with carcinogenesis, and other biological effect markers identified in preclinical studies. ? Develop further scientific insights into the mechanisms of cancer prevention by the agents studied and to develop novel potential markers as determinants of response and for selecting subpopulations who may differentially benefit from the studied agent. Through the proposed research, we expect to conduct rigorously designed early phase cancer prevention clinical trials that determine the clinical activity and biological effects of potential preventive agents. The research findings will further scientific insights into the mechanisms of cancer prevention and develop novel potential biomarkers as determinants of response. Scientific and clinical evidence generated from these early phase cancer prevention clinical trials will contribute significantly to ?go-no go? decisions for further clinical development of putative agents for cancer prevention.